Clinical Trial: Prospective Pilot Trial to Assess a Multimodal Molecular Targeted Therapy in Children, Adolescent and Young Adults With Relapsed or Refractory High-grade Pineoblastoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Prospective Pilot Trial to Assess a Multimodal Molecular Targeted Therapy in Children, Adolescent and Young Adults With Relapsed or Refractory High-grade Pineoblastoma

Brief Summary: Children, adolescents and young adults with relapsed or treatment refractory pineoblastoma (rPB) represent a group of patients with dismal prognosis for whom a recommended standard salvage therapy is currently not available.

Detailed Summary:

The multimodal metronomic approach combining molecular targeted drugs (rapamycin and dasatinib) with conventional chemotherapy (irinotecan and temozolomide) will be investigated in a randomized fashion as new treatment strategy for patients with rPB. The intention is to assess the therapeutic benefit of molecular targeted drugs for the treatment of rPB.

The combination of irinotecan and temozolomide showed activity in the treatment of several solid organ tumors, brain tumors and neuroblastoma. In one study relapsed neuroblastoma (rNB) patients received a median of 5 courses of 5 days irinotecan and temozolomide every 3 to 4 weeks with a cumulative dose of 35% lower than in the RIST design. 33% had disease regression with 8% CR or PR. A phase II study in rNB also using irinotecan and temozolomide with a substantially lower intensity showed a response rate of 15%.

The combination of a mTOR inhibitor with a multi-kinase inhibitor demonstrated in preclinical studies a synergistic effect on cell cycle arrest, apoptosis and sensitization for radio- and chemotherapy. It is assumed that this combination of molecular targeted drugs with a tolerable conventional chemotherapy consisting of irinotecan and temozolomide can substantially improve the outcome of this patient population. A group of 20 rNB patients treated with the RIST therapy approach in a compassionate use setting showed an overall survival of 55% at a median of 80 weeks with a tolerable adverse event profile.


Sponsor: University of Regensburg

Current Primary Outcome: The primary endpoint is progression-free survival (PFS) [ Time Frame: Time interval from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks ]

According to:

  • Imaging criteria to

    • MRI, CT or
    • CSF evaluations or
  • date of death of any cause


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Overall survival (OS) [ Time Frame: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks ]
    According to: questionnaire
  • Response to the investigational treatment after 4 and 8 courses of I/T and 1-year-follow-up in the RIST treatment arm [ Time Frame: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks ]

    According to:

    • Imaging criteria to

    • MRI, CT or
    • CSF evaluations
  • Duration until adequate response to this treatment regimen [ Time Frame: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks ]

    According to:

    • Imaging criteria to

    • MRI, CT or
    • CSF evaluations
  • Assessment of quality of life (Lansky and Karnofsky Scores) [ Time Frame: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks ]

    According to:

    Lansky and Karnofsky Scores

  • Toxicity of this combination of drugs in children, adolescents and young adults with rNB - Assessment according to the latest version of the CTC criteria [ Time Frame: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks ]

    Assessment according to the latest version of the CTC criteria. In particular due to the expected AE Profile:

    Myelosuppressive measures (RBC, PLT units) Infectious complications Gastrointestinal problems

  • Safety and tolerability of the investigational treatment - Assessment according to the latest version of the CTC criteria [ Time Frame: From the first course of the investigational treatment up to the end of the trial assessed to 52 weeks ]

    Assessment according to the latest version of the CTC criteria. In particular due to the expected AE Profile:

    Myelosuppressive measures (RBC, PLT units) Infectious complications Gastrointestinal problems



Original Secondary Outcome: Same as current

Information By: University of Regensburg

Dates:
Date Received: October 28, 2015
Date Started: April 2016
Date Completion: April 2020
Last Updated: December 29, 2016
Last Verified: December 2016